The use of adjuvants in vaccines is well known. An adjuvant is a compound that, when combined with a vaccine immunogen, increases the immune response to the vaccine immunogen. Among strategies that promote immunogenicity of a protein, glycoprotein or peptide are those that emulsify vaccine immunogens. (Nossal 1999, In: Fundamental Immunology. Paul (Ed.), Lippincott-Raven Publishers, Philadelphia, Pa.; Vogel and Powell, 1995, In: Vaccine Design. The Subunit and Adjuvant Approach. Powell and Newman (Eds.), Plenum Press, NY, N.Y. p. 141). Because of the essential role that adjuvants play in improving the immunogenicity of vaccine immunogens, the use of adjuvants in the formulation of vaccines has been virtually ubiquitous (Nossal, 1999, supra; Vogel and Powell, 1995, supra; the teachings of which are incorporated herein by reference). Conventional adjuvants, well-known in the art, are diverse in nature. They may, for example, consist of water-insoluble inorganic salts, liposomes, micelles or emulsions, i.e. Freund's adjuvant. Other adjuvants may be found in Vogel and Powell, 1995, mentioned supra. Although there is no single mechanism of adjuvant action, an essential characteristic is their ability to significantly increase the immune response to a vaccine immunogen as compared to the response induced by the vaccine immunogen alone (Nossal, 1999, supra; Vogel and Powell, 1995, supra). In this regard, some adjuvants are more effective at augmenting humoral immune responses; other adjuvants are more effective at increasing cell-mediated immune responses (Vogel and Powell, 1995, supra); and yet another group of adjuvants increase both humoral and cell-mediated immune responses against vaccine antigens (Vogel and Powell, 1995, supra).
Generally, emulsions used in vaccine formulation comprise a mixture of oil, aqueous solution and surfactants. Some emulsions incorporate a lipophilic surfactant such as Span 80® and a hydrophilic surfactant such as Tween 80®. These emulsions may also contain compounds such as lecithin or saponin known to have ionic surfactant properties.
However, problems of stability can be observed with emulsions used as vaccine adjuvants, in particular during storage or transport. Lipase or esterase enzymatic activities present in the solution or suspension of immunogen can hydrolyse the surfactants of the emulsion and can lead to a lack of stability of the adjuvant. The lipases or esterases can come for example from the cell culture used to grow viruses or from bacteria This is particularly true when these compositions contain concentrated immunogens, especially non-purified concentrated immunogens. Typically, this is the case with adjuvants used in inactivated (killed) vaccines. This problem is even more significant with multivalent vaccine compositions because the immunogens are more concentrated in the same volume of diluent.
Another problem with adjuvant use is linked to a risk of adverse events such as toxicity or local inflammation at the site of injection. For example, a local inflammatory response and/or granulomae may result after injection. In order to limit such an adverse reaction, surfactants and other components in the emulsion may be reduced; however, the reduction may then result in a decrease in the stability of the vaccine composition. There is, therefore, a need for novel adjuvants and vaccine compositions containing such adjuvants with increased safety and stability.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.